From the beginning of recorded time people have made efforts to promote good health in humans and animals. The efforts to promote good health include the identification of compositions such as drugs which treat diseases. However, a preferable approach is to identify preventative measures which reduce the likelihood of pathological conditions. In this regard it is particularly advantageous to identify preventative methods which can be readily practiced by all people without side effects. Unfortunately, such beneficial preventative measures have proven to be very illusive, as evidenced by the high incidence of cancer, heart disease and other pathologies in our society.
For many years now, considerable research and resources have been devoted to the study of oncology and the identification and development of materials and methods for the control of cancer. The methods which have been investigated include radiation, chemotherapy, herbal medicines and holistic approaches. While certain methods and chemical compositions have been developed which aid in inhibiting, remitting, or controlling cancer, new methods and anticancer chemical compositions are needed.
In searching for new biologically active compounds, it has been found that some natural products and organisms are potential sources for chemical molecules having useful biological activity. For example, the diterpene commonly known as taxol, isolated from several species of yew trees, is a mitotic spindle poison that stabilizes microtubules and inhibits their depolymerization to free tubulin (Fuchs, D. A., R. K. Johnson [1978] Cancer Treat. Rep. 62:1219–1222; Schiff, P. B., J. Fant, S. B. Horwitz [1979] Nature (London) 22:665–667). Taxol is also known to have antitumor properties and has undergone a number of clinical trials which have shown it to be effective in the treatment of a wide range of cancers (Rowinski, E. K. R. C. Donehower [1995] N. Engl. J. Med. 332:1004–1014). See also, e.g., U.S. Pat. Nos. 5,157,049; 4,960,790; and 4,206,221.
Marine sponges have also proven to be a source of biologically active chemical molecules. A number of publications have been issued disclosing organic compounds derived from marine sponges including Scheuer, P. J. (ed.) Marine Natural Products, Chemical and Biological Perspectives, Academic Press, New York, 1978–1983, Vol. I–V; Uemura, D., K. Takahashi, T. Yamamoto, C. Katayama, J. Tanaka, Y. Okumura, Y. Hirata (1985) J. Am. Chem. Soc. 107:4796–4798; Minale, L. et al. (1976) Fortschr. Chem. org. Naturst. 33:1–72; Faulkner, D. J. (1987) Natural Products Reports 4:539–576, and references cited therein.
The role of diet in maintaining optimal health in a subject, and in slowing or reversing the progression of disease has been the subject of much public attention and commercial enterprise. The term “nutriceutical” is intended to describe specific chemical compounds found in foods that may prevent disease. The term “phytochemical” emphasizes the plant source of most of these protective, disease-preventing compounds. Relatively little is known about the biological effects of phytochemicals, but it is widely believed that this group of compounds will assume a role similar to common multi-vitamins in the future. Where data is available, it is usually derived from long-term epidemiological studies of humans, or studies in animals with diet regimens. Current studies are showing that as we move away from the diet of our ancestors we succumb to modern diseases. Evidence for this is seen in societies that live in remote villages and who still embrace traditional dietary practices yet remain relatively free of modern diseases, such as cancer.
For example, epidemiological studies strongly suggest a protective role for diet rich in fruits and vegetables against lung cancer. Studies have shown a marked differential in the rates of lung cancer in the islands of the South Pacific, independent of cigarette smoking (Loic Le Marchland, et. al., (1989) “Vegetable consumption and Lung Cancer: A Population-Based Case-Control Study in Hawaii”, J. Natl. Cancer Institute, 81:1158; and Loic Le Marchand, et. al., (1995) “An Ecological Study of diet and Lung Cancer in the South Pacific”, Int. J. Cancer: 63:18). Consumption of a variety of fruits and vegetables is thought to partly explain this difference.
Dietary components such as soluble fibers and flavonoid agents have been suggested as having beneficial effects in reducing the risk of cancer (Franke, Adrian A., Robert V. Cooney, Laurie J. Custer, Lawrence J. Mordan, Yuichiro Tanaka (1988) “Inhibition of Neoplastic Transformation and Bioavailability of Dietary Flavonoid Agents” Advances in Experimental Medicine and Biology 439:237).
Retinoids have been shown to inhibit carcinogenesis in many experimental systems (Moon, R. C., (1989) “Comparative Aspects of Carotenoids and Retinoids as Chemopreventive Agents for Cancer”, J. Nutr., 119:127) and in humans, to prevent neoplasia (cancer) or to revert precancerous lesions at several anatomical sites (Hong, W. K., et al., (1990) “Prevention of Second Primary Tumors with Isotretinoin in Squamous Cell Carcinoma of the Head and Neck”, NEJM, 323:795; and Alfthan, O., et. al., (1993) “Etretinate in Prevention of Recurrence of Superficial Bladder Tumors: A Double-blind clinical Trial”, Eur. Uro., 9:6).
Researchers have stated that various natural carotenoids, which co-exist with beta carotene in fruits and vegetables, have anti-carcinogenic activity, especially lycopene and lutein (Nishino, H., (1997) “Cancer Prevention by Natural Carotenoids”, J. Cell Biochem. Suppl., 27:86 and “Cancer Chemoprevention by Natural Carotenoids and their Related Compounds”, J. Cel Biochem. Suppl., 22:231). Carotenoids generally refer to a class of labile, easily oxidizable, yellow, orange, red, or purple pigments, which are lipid in character, and widely distributed in plants.
Some phytochemicals may be categorized as anti-oxidants, vitamins which neutralize free radicals (molecules with unpaired electrons). Free radicals attack cells and damage tissues resulting in premature aging, reduced immune function, inflammation and ultimately degenerative disease. The hydroxyl radical (OH•), an oxidizing agent produced by the degradation of hydrogen peroxide and molecular oxygen, is regarded as being the most damaging species. Aging and deterioration in human cells is caused by the chemical process of oxidation. Scientists theorize that when pollutants, chemicals, and toxins such as cigarette smoke or food additives combine with oxygen in the bloodstream, unstable free radicals are produced. Free radicals then weaken cell membranes, inviting disease and infection. Anti-oxidant nutrients, such as vitamin C and E, are the body's primary defense against free radicals. Anti-oxidants restrict the supply of oxygen to the free radicals, neutralizing them. Therefore, the cells and tissues remain younger and healthier.
The present invention has added to the arsenal of anticancer compositions by the discovery of organic compositions possessing anti-oxidant activities. These compositions can be isolated from extracts of mangos. Other health-promoting benefits of the compositions of the subject invention are set forth below with particularity.